Natural products represent a pool of privileged structures that are optimized by evolution to interact with proteins and other biomolecules. The enormous structural diversity of natural products thus provides an indispensable resource in an effective search for new therapeutic agents. Plants are of particular interest as source of pharmaceutically active compounds since they are used to treat diseases and maintain health since prehistoric times. They produce an enormous variety of substances that play a role in the plant defense mechanisms against predation by microorganisms, insects, and herbivores. The classical phytochemical approach in drug discovery focuses on secondary metabolites such as glycosides, phenolics, carbohydrates, alkaloids and terpenoids. The therapeutic potential of plant peptides and proteins, on the other hand, is by far less well studied and has only recently gained broader interest. The main reason for this is that standard proteomic and metabolomic approaches are not suitable for a systematic peptide analysis. For that reason, we are aiming at developing a peptidomic workflow using ultra-high performance chromatography and state-of-the-art mass spectrometry to cover the mass range of interest for the detection of plant peptides. The focus of the proposed project is the identification, isolation and characterisation of novel pharmacologically active peptides and mini-proteins from different plant species. Of particular interest are small (less than 100 amino acid residues), cysteine-rich peptides and proteins (CRPs), and in particular cyclotides, that often show remarkable antimicrobial, antifungal, antiviral and insecticidal activity as well as other pharmacologically interesting effects.
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